Tfflazolone berivative



United States PatentQ THIAZOLON E DERIVATIVE Edward B. Knott, Harrow,'England, assignortoEastman Kodak Company, Rochester, N. Y., a corporation of New-Jersey No Drawing. Application September 16,1953, Serial No.380,603

1 Claim. (Cl. 260306.7)

This invention relates to intermediates useful in the preparation of optical sensitizing dyes and methods of.

making thesecn'ew intermediates.

The new compounds" of my invention can advantageously berepresented by the followinggeneral formula:

wherein R represents an alkyl group, such as methyl,

ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-amyl, nhexyl, n-heptyl, n-octyl, n-lauryl, benzyl (phenylmethyl), carbethoxymethyl, etc. ((2. g. an alkyl group of the formula C1LH21L+1 wherein n represents a positive integer of from 1 to 12), or anaryl group, such as phenyl, 0-, mandp-tolyl, etc. (e. g. a mononuclear aromatic group of the benzene series), andQ represents the non-metallic.-

atoms necessary tocomplete a thiazole nucleus, such as a 2-thiothiazolid-4-one nucleus (i. e. a rhodanine nucleus), a thiazole-S-one nucleus, etc.

Accordingly, it'isLan object ofmy invention to provide newintermediates usefulin the preparation of optical sensitiz'ingdyes. A further object is to'providera method for making these new intermediates. Other objects will become apparent from a consideration of the following description and examples.

Advantageously, I provide the new compounds rep-- resented by Formula I above by condensing a compound selected from those represented by the following general formula:

ni-o-c c wherein R1 represents a lower. alkyl group, e. grmethyl, ethyl,. etc.,.and.Q has:.the values given. above, witha mercaptan .selectedfrom those represented by. the: following general formula:

RAH

wherein R has the values given above. The condensations are carried out in the presence of zinc chloride as:

a Jcatalyst, the zinc chloride being usedin conjunction with dry hydrogen chloride. Thus, the reaction is carried out under substantially anhydrous conditions.

The reaction or condensation can be accelerated by heating, although'Thave foundthatthe'reaction proceeds at room temperature When-the reactants are allowed to stand mixed together. Advantageously, I have found that the condensation proceeds smoothly in' the" presence of an inerrsolvent, such as'dio'xan, diethyl ether, petroleum ether, etc; When using such an inert'diluent, thereac't'ionxcan be accelerated by'heating thereaction mixture under constant reflux conditions. Thequantity ofreactants can be varied, although I have found that it is generally advantageous'to use an'excess of mercaptan n l yl sr p.

over the -molecular quantity required forth'e condensa tion; In general; from 1 to3 molecular equivalents" of 2,739,970 Patented .Ma-r.-.2 7, .1956

2,728,766, issued December 27, 1955). Useful mer- .captans embraced by IIIabove-include, for example,

methylmercaptan, ethylmercaptan, n-propylmercaptan, isopropylmercaptan, n-butylmercaptan, isobutylnrercaptan, n-amylmercaptan, n-hexylmercaptan, n-heptylmercaptan, n-octylmercaptan, n-laurylmercaptan, benzylmercaptan, ethylmercaptoacetate, etc.

Especially useful '2-thiothiazolid-4-ones obtainable according to my invention comprise th'oserepresented by the following general formula:

wherein R has the values given above and R2 represents an alkyl group, .such as methyl, ethyl, n-propyl, n-butyl, al'lyl' (vinylmeth'yl), carbethoxyrnethyl, benzyl (phenylmethyl), etc; or 'acycl'oalkyl group, such as cyclopentyl, cyclohexyl, etc. The compounds of Formula IV are advantageously, prepared .by condensing a compound selected from those represented by the following general wherein R1. andRz-each' havedhe values given. above with a mercaptan selected from those. representedby Formula IILabove.

Especially usefulthiazol-fi-ones obtainable according to my invention comprise those represented by the following general formula:

wherein-.Rhas the valuessgivenabove andRs. represents such as a methyl, benzyl (phenylmethyl etc. The-compounds; selected-from those. represented by Formula .VI. can. advantageously be. prepared. by. condensing a\compound.selected.from .those represented by, the

wherein R1 and R3 each have the values given above, with a mercaptan'selected from those. represented by Formula III above; The condensation of the compounds selected from those represented by Formula V with those represented by Formula III, and the condensation of the compounds selected" from those represented 'by Formula VII'With those'o f'Formula III are performed under. substantiallythe'same conditions as those, described above forthecond'ensation of the compounds of Formula-II witlrthose'ofFormula'III, i. e; the compounds ofFormula V and tlioseof Formula VII are species 'of the*compounds represented by Formula-II.

The following examples will serve to illustrate more fully the manner whereby I practice my invention.

Example 1. 3 carbethoxymethyl-j-(I'-ethylthioethylidene)-2-thiothiazolid-4-one 3-carbethoxymethyl-5-( l'-ethoxyethylideue)-2 thiothiazolid-4-one (2.9 g., 0.01 mol.), ethylmercaptan (1.5 cc., 0.02 mol.), powdered zinc chloride (2.7 g., 0.02 mol.) and dioxan cc.) were saturated at room temperature with dry hydrogen chloride. The mixture was then set aside for 18 hours and poured into water (100 cc.). The orange oil which precipitated, rapidly solidified. It (3.0 g., 98%) formed yellow flakes, M. P. 67-69 C., from isopropanol or light petroleum (B. P. 60-80 C.).

Example 2 .-3-carbeth oxymethyl-S- 1 '-isopropylthioeth ylidene -2-th i-othiazolid-4-one This compound was obtained according to the process of Example 1, but using isopropylmercaptan (1.5 cc.). It (1.75 g., 54.5%) was obtained as pale yellow flakes, M. P. 107-108 C., from light petroleum (B. P. (SO-80 C.) or isopropanol.

This compound was obtained according to the process of Example 1, but using n-butylmercaptan (1.5 cc.). It (2.75 g., 82.5%) was obtained as jagged needles, M. P. 92-93 C. together with a second fraction, M. P. 62-92 C. (yellow needles).

Ha S

3-allyl-5-(1'-eth0xyethylidene)-2-thiothiazolid 4 one (2.45 g.), p-thiocresol (1.25 g.), powdered zinc chloride (2.7 g.) and dioxan (20 cc.) were saturated with dry hydrogen chloride and set aside overnight. Precipitation with Water gave an oil which slowly, partially solidified. After repeated recrystallization from isopropanol it was obtained as fiat, cream needles, M. P. 90 C.

Example Example Example 4 I 6 .-3-carbethoxymethyl-5 I '-p-tolylthioethylidene)-2-thiothiazolid-4-one Example maga g a.

CH: N

4-( l-ethoxyethylidene) -2-ethylthiothiazol-5-one (Aubert, Knott and Williams, J. Chem. Soc., 1951, 2185) was obtained crude as a brown oil by heating N-dithiocar-bethoxyglycine (18.0 g.), acetic anhydride cc.) and ethyl orthoacetate (50 cc.) on to steam bath for 1 hour followed by removal of the solvents under'reduced pressure. It was then extracted with light petroleum (B. P. 60-80 C.) the slight residue discarded and the solvent removed. It distilled as a light orange oil, B. P. 132-l34 C./2 mm.

The above (21.9 g.), and ethylmercaptan (15 cc.) were dissolved in dioxan (30 cc.), powdered anhydrous zinc chloride (27 g.) was added and the whole saturated with hydrogen chloride. After standing 18 hours the required substance was precipitated as an orange oil by the addition of water (150 cc.). It was taken up in ether, dried and the solvent removed to leave 23.0 g. of orange oil.

Example N-dithiocarbobenzyloxyglycine (48.2 g.), ethyl orthoacetate (100 cc.) and acetic anhydride (200 cc.) were heated at -l30 C. for 1 hour and the solvents removed. The residual oil was distilled and 18.7 g., 32% collected at 208 C./1 mm.

The orange oil (5.85 g.) and ethylmercaptan (3 cc.) were dissolved in dioxan (25 cc.), powdered anhydrous zinc chloride (5.4 g.) was added and the whole saturated with dry hydrogen chloride. The solution was stood 18 hours and the required substance thrown out as an oil by the addition of water (100 cc.). It was taken up in ether, dried and the ether removed to leave 5.9 g. yellow oil suitable for dye condensations.

Example 9.3-cycl0hexyl-5-(1'-ethylthi0ethylidene)- 2-thiothiazolid-4-one crystallizations. The filtrate gave a product as yellow needles, M. P. 8991 C. from light petroleum or isopropanol. This was distilled to give a product (B. P. 170 C./3 mm.) which crystallized to yellow needles, M. P. 60-61 C. which represented the desired product.

Example 10.-(1 '-benzylthioethylidene)-3-carbeth0xymethyl-Z-thi0thiaz0lid-4-0ne 3-carbethoxymethyl-5-(1'-ethoxyethylidene) 2 thiothiazolid-4-one (5.8 g.), and benzylmercaptan (2.5 cc.) were dissolved in dioxan (25 cc.) and powdered anhydrous zinc chloride added. On saturating with dry hydrogen chloride the temperature rose to 60 C. After standing overnight the solution was treated with water (100 cc.). The brown oil partially crystallized on chill ing. From ethanol (100 cc.) yellow crystals, M. P. 82-95 C. (3.4 g., 46.3%) were obtained. The filtrates giving an oil on concentration. The crude crystalline mixture of cisand trans-isomers is suitable for dye condensations. One isomer, pale yellow flakes, M. P. 99-100 C. was isolated on repeated recrystallization from ethanol.

Example 11.--3-carbethoxymethyl-5-(1 '-n octylthioethylidene)-2-thi0thiaz0lid-4-0ne 3-carbethoxymethyl-5-( 1'-ethoxyethylidene) -2-thiothi azolid-4-one (2.9 g.), n-octylmercaptan 1.5 g.), powdered anhydrous zinc chloride (2.7 g.) and dioxan (20 cc.) were saturated with dry hydrogen chloride and stood for 72 hours. Water (100 cc.) was added, the orange oil taken up in ether, dried and the solvent removed. The residual oil was suitable for dye condensations.

It may be distilled as an orange oil by 232-240 C./2.5 mm. the oil crystallizing as long orange needles. Example 12.3-ethyl-5-(1'-ethylthi0ethylidene)-2 thio- 3-ethylrhodanine (20 g.), ethylorthoacetate (50 cc.) and acetic anhydride (100 cc.) were refluxed for 4 hours and the solvents removed under reduced pressure. The residual oil solidified on chilling. From isopropanol a yield of 14.6 g. (51%) of orange needles, M. P. C. was

obtained, the M. P. remaining at 80 C. on further recrystallization.

The above (4.6 g.), ethylmercaptan (2 cc.), powdered anhydrous zinc chloride (5.4 g.) and dioxan (20 cc.) were saturated with dry hydrogen chloride and stood for 12 hours. The deep yellow solution was then poured into water and chilled. The orange oil did not crystallize on chilling, it was taken up in ether, dried, and the ether removed. The orange oil which was obtained in a yield may be used directly for dye condensations. On prolonged standing, it partially crystallizes; then crystals freed from the oil form yellow needles, M. P. 97 C. from isopropyl alcohol; yield 1.2 g.

As shown in application Serial Nos. 309,743 and 343,- 809, the compounds of Formula II can be prepared by condensing a ketomethylene compound together with an alkyl orthoacetate. However, attempts to prepare the corresponding sulfur compounds using an alkyl trithioacetate did not provide an eflicient means of preparing the compounds represented by Formula I, although these esters were obtained in small quantities in certain instances. The present process provides an eflicient means of preparing the compounds of Formula I, the intermediates being obtained in pure form and in condition for dye condensations. In some instances, the process of the instant invention results in the formation of cis and trans isomers. As shown in the above examples, it is sometimes possible to separate these isomers from one another, although this is not usually necessary for the preparation of optical sensitizing dyes for which the in stant intermediates are particularly useful. The intermediates of the instant invention can also be used in the preparation of other organic compounds, such as antibiotics and the like.

What I claim as my invention and desire secured by Letters Patent of the United States is:

The compound having the following formula:

O=C-S G:H5SC=(IJ -S-CH2CoHs References Cited in the file of this patent UNITED STATES PATENTS 2,535,276 Edwards et al. Dec. 26, 1950 2,658,890 Croxall et al. Nov. 10, 1953 FOREIGN PATENTS 557,550 Great Britain Nov. 25, 1943 OTHER REFERENCES Brown et al.: J. Org. Chem., vol. 15, pp. 174-6 (1950). 

